The recanalization of brain following ischemic stroke is the best means of recovering brain. However, restoration of flow is often accompanied by brain injury and tissue death. A reliable depiction of restoration of flow together with salvageable brain is of clinical significance. Imaging with MRI offers diagnostically useful depictions of stroke injury from T2, DWI, and perfusion imaging. However, we need improved methods of perfusion in order to best map and differentiate flow from tissue status. The clinical hypothesis that reperfusion of brain is a process of restoration of flow in the time window of salvaging brain, and being able to depict both aspects of that reperfusion process are crucial to the hundreds of reperfusion procedures done daily worldwide. The overall goal of this new submission is to identify and improve cerebral blood flow (CBF) techniques from dynamic susceptibility contrast (DSC) perfusion-weighted MRI (PWI) methods that can depict both restoration of flow together with the microvascular status that would optimally compare with DWI to form a clinically useful DWI-PWI mismatch representing brain tissue-at-risk or salvageable brain. To do this, we will assess the value of mapping perfusion with a gradient- echo (GRE) and a spin-echo (SE) signal acquired together in a multi-shot, multi- echo, and DSC first-pass bolus contrast agent MRI technique. The perfusion maps will be compared with a gold-standard xenon CT (xeCT) value of CBF. We aim to show equivalence between GRE- and SE-DSC to the gold-standard in order to visualize vascular and microvascular status in 120 stroke patients having had recanalization procedures. We will obtain T1, T2, T2*, diffusion-weighted imaging (DWI), and bolus PWI in 120 patients presenting at 6-48 hours following reperfusion and obtain a second follow-up study at 30 days as a measure of tissue outcome together with clinical assessments. We believe successful attainment of these aims promises to markedly improve acute stroke care by validating a MRI-based perfusion methods sensitive to both vascular status and tissue microvascular status. This study will lead to better understanding of mapping flow and microvascular status in patients with severe cerebrovascular disease and greatly enhance the already significant diagnostic power of MRI in acute ischemic stroke by better mapping metabolic- perfusion mismatches after reperfusion. PUBLIC HEALTH RELEVANCE: In the early hours following large vessel occlusion, the ultimate severity of the stroke will be greatly determined by how long the occlusion has gone on and how soon the vessels can be opened and flow restored to the brain. One question however, is how to depict the regions of the brain suffering from the stroke that will be recovered by restoration of flow and which parts will eventually die. This proposal assesses whether a rapid means of acquiring blood flow data from MRI can accurately and reliably measure the blood flow in various parts of the brain and whether this MR method can see recoverable brain from regions of the brain destined to die. The do this, we will compare various MRI methods of mapping blood flow with known standards in radiology. These MRI-based methods use an injected contrast agent that can give maps of blood flow, blood volume, transit time of the blood, arrival times of the blood flow and other measures of vascular status. They can also depict flow that is sensitive to all vessels including the larger feeding arteries to the stroked region as well as the small capillary beds necessary for delivering oxygen to the brain tissue. We will include 120 stroke patients into this study that have had reperfusion procedures done within a time window of 6 to 48 hours. For all patients, we will validate the MRI cerebral blood flow measurements using a gold-standard, stable xenon-enhanced CT exam. Successful completion of this project will lead to better understanding of how well MRI can measure blood flow and which MRI measurement will give us the best view of brain regions that have had flow restored after recanalization (or reperfusion) and which regions are likely to die even after restoration of flow. This will greatly enhance the already significant diagnostic power of MRI in acute ischemic stroke.